title: A dual-responsive mesoporous silica nanoparticle for tumor-triggered targeting drug delivery.
abstract: A novel pH- and redox- dual-responsive tumor-triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox-responsive, as a gatekeeper as well as a tumor-targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic-imine bond, which is pH-sensitive, are then connected via "click" chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic-imine bond under acidic conditions. After deshielding of the MPEG segment, the drug-loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010455:Peptides / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013818:Thermogravimetry
chemical_list: D010455:Peptides; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: drug delivery; pH-responsive; peptides; redox-responsive; tumor-triggered target